Glycosylated Polymers as Carriers for Targeting Antiviral and Antiparasite Drugs

Abstract

A therapeutic agent to be active must reach its target cell and more precisely the right compartment of the target cell. For a great majority of drugs, the compartment is either the cytosol or the nucleoplasm. When hydrophobic, a drug may cross the plasma membrane to enter the cytosol. However when hydrophilic, a drug is not membrane permeant and usually will enter the cytosol from an intracellular organelle. On these bases, drug targeting may enhance the efficacy of a hydrophilic drug. The rationale of drug targeting using macromolecular glycoconjugates includes the following considerations:

a small molecular weight hydrophilic drug is usually lost in vivo within a few minutes, while bound to a macromolecular carrier it will stay longer in the blood,

a macromolecular carrier containing carbohydrate moieties as a recognition signal will be recognized by cell surface receptors (lectins) with a specificity depending on the nature of the carbohydrate moiety used and on the type of lectin present on the target cell. Therefore the amount of drug at the level of the target cell will be much higher than when the free drug is used,

a carbohydrate moiety used as recognition signal allows the binding and the internalization of the drug-carrier conjugate because membrane lectins usually mediate endocytosis,

the drug must be attached to the carrier in such a way that it will be linked until its release in a selected organelle inside the target cell.